Project Summary/Abstract Pregnant women with PTSD are more likely to experience preterm birth and perinatal mental health problems. However, underlying mechanisms explaining these associations are not well understood. PTSD- related neurobiological factors, such as allopregnanolone and pregnanolone (together termed ALLO), are promising underlying mechanisms. ALLO is: a) a neuroactive metabolite of progesterone, b) lower among women with PTSD, and c) has been linked to preterm birth in animal models. Psychosocial factors may modulate neurobiological risk; exposure to intense stress and social isolation reduces ALLO levels in animal models. The proposed study will examine the role of neurobiological and psychosocial factors contributing to risk for both preterm birth and increased maternal mental health symptoms during pregnancy and the postpartum among women with PTSD ? a highly relevant aim to the mission of NICHD. The candidate will prospectively follow 150 pregnant women (60 with PTSD, 60 trauma-exposed without PTSD, and 30 non-trauma exposed healthy controls) receiving care in an inner city obstetrics clinic. Regular assessment of PTSD and depressive symptoms, psychosocial stressors and support, and neurohormones (e.g., ALLO) will be made throughout pregnancy and at 6 weeks postpartum. This study will examine whether: 1) deficient ALLO mediates the effects of PTSD group status (PTSD vs. trauma exposed no PTSD vs. healthy) on preterm birth and increased maternal PTSD/depression during pregnancy and the postpartum, and 2) social support moderates the relationship between stress and deficient ALLO across pregnancy and the postpartum. The candidate's career goal is to conduct transdisciplinary and translational research that will: a) identify interactive psychological and neurobiological mechanisms related to negative obstetric outcomes, b) use this information to develop assessment and intervention efforts, and c) implement these assessment and interventions within an existing medical care system. To accomplish these goals, additional training in: a) PTSD-related neurobiology, b) obstetrics and reproductive mental health, c) advanced statistical methods, d) grant writing, and e) professional development, is needed. The multidisciplinary team of mentors, consultants, and advisors will provide expertise in PTSD-related neurobiology, obstetrics, reproductive mental health, psychosocial risk, and advanced statistical methods. These mentors, along with the outstanding resources at Boston University and VA Boston, will ensure the candidate the requisite support to meet her goals. This innovative project translates findings from animal research to a clinical setting, integrates information across disciplines, and aims to identify shared mechanisms for preterm birth and psychopathology. This study will produce novel findings that will enable the candidate to submit an R01 testing novel pharmacological and psychosocial interventions targeted to at-risk subgroups via a precision medicine approach.